|
author |
Thomas Potts
| title |
Interactions Between IFI16 and Chromatin Silencing Proteins
| abstract |
Interferon-inducible protein 16 (IFI16) has classically been described as a
cytosolic viral DNA pattern recognition receptor (PRR) that begins a signaling pathway
to lead to the production of interferon β (IFN-β) in response to viral infection. However,
it has also been shown to have other, noncanonical antiviral roles, such as promoting the
silencing of integrated HIV. DNA editing protein APOBEC3A (A3A) and the chromatin
remodeling complex human silencing hub (HUSH) have both been shown to also be
involved in the silencing of HIV, specifically via chromatin methylation. However, the
DNA sensor that is used for this response has not been shown. We propose that IFI16 is
that sensor. In this study, we conduct immunoprecipitation (IP) experiments with a
nuclease to show evidence of direct protein-protein interactions between IFI16 and
APOBEC3A. We also show evidence of a similar, although more complex and
interesting, relationship between IFI16 and TASOR, a member of the HUSH complex,
which only occurs in the absence of nucleic acid. These findings suggest that IFI16 exists
in pathway(s) with APOBEC3A, TASOR, or both that could result in the silencing of
viral DNA. These suggest implications in the treatment of retroviruses such as HIV with
new targets for antiretroviral therapies (ARTs).
| school |
The College of Liberal Arts, Drew University
| degree |
B.S. (2020)
|
advisor |
Brianne Barker
|
full text | TPotts.pdf |
| |